This is a highly sophisticated analysis of the post-Paxlovid rebound phenomenon and its clinical significance. NIH investigators used viral sequencing and culture, serologic data, T-cell stimulation assays and soluble biomarkers in an 8-patient cohort of mostly Omicron BA.2 breakthrough infections who exhibited rebound and a 7-patient infected control group who did not.

Robust cytokine-producing, proliferating, activated SARS-CoV-2–specific T-cell responses were greater during rebound than during early acute COVID-19, along with rising T-cell counts. Anti-nucleocapsid IgG and Omicron-specific neutralizing antibodies were also increased in 6 patients with rebound symptoms.

This suggests that clinical rebound may be an indicator of a robust immune response rather than uncontrolled viral replication driving inflammation or a significant risk of impending disease progression. No patient developed severe disease during rebound, and adaptive immunity against SARS-CoV-2 appeared intact.

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac663/6749408